DNA Structure, Replication, Repair, and Genome Stability
Architecture of the Genome
DNA chemistry and topology
DNA is a chemically simple polymer with profound informational density. Its antiparallel strands, base pairing, major and minor grooves, and supercoiled topological states underpin replication, transcription, and chromatin organization. Genome maintenance requires coordination between polymerases, helicases, primases, ligases, topoisomerases, and repair enzymes.
Core replication components
Replication fidelity
High fidelity arises from substrate selectivity, proof-reading exonuclease activity, and mismatch repair. The combined error rate can approach to errors per base per division in many systems, though this varies by organism, genomic context, and polymerase usage.
Conceptual trap
Replication is not merely copying; it is a regulated process integrated with origin licensing, cell-cycle checkpoints, chromatin state, and DNA damage surveillance.
Types of DNA repair
Base excision repair
- Fixes small base lesions
- Uses glycosylases and AP endonucleases
- Important for oxidative damage
Nucleotide excision repair
- Removes bulky adducts and UV lesions
- Excises a short oligonucleotide segment
- Critical for genome integrity
Which process most directly increases replication processivity?
Sliding clamps tether polymerase to DNA, allowing long continuous synthesis.
Correct answer: Sliding clamp loading
What is the role of proofreading exonuclease activity?
Proofreading is a key determinant of replication fidelity.
Correct answer: It removes misincorporated nucleotides during replication
Which repair pathway primarily corrects UV-induced thymine dimers in many organisms?
Bulky UV lesions are classically repaired by nucleotide excision repair.
Correct answer: Nucleotide excision repair
Why are topoisomerases essential during replication?
Without topological control, fork progression stalls and DNA can become damaged.
Correct answer: They relieve torsional strain and supercoiling ahead of the replication fork